Human sex reversal is caused by duplication or deletion of core enhancers upstream of SOX9

Initial steps in the sex determination of the (human) testis depend on SRY regulating SOX9, but the exact mechanism that controls SOX9 expression remains unknown. These authors discovered four overlapping copy number variations (CNVs) upstream of SOX9 as the causes of sex reversal in two 46,XX DSD (with duplications) and two 46,XY DSD patients (with deletions). Prompted by this, they performed studies of these CNVs in cell systems and in mice, and found three essential regulatory elements for normal testis and male sex development, namely eSR-A, eSR-B and eALDI.